The frequency of T cell receptor (TcR) type and the variable gene segment expression in human intraepithelial lymphocytes (IEL) from the large intestinal mucosa were studied by flow cytometry and immunohistochemistry, and compared to those in peripheral blood lymphocytes (PBL) — or lamina propria lymphocytes (LPL). Employing anti‐γ/δ TcR and anti‐α/β TcR monoclonal antibodies (mAb), flow cytometric analysis revealed that a large fraction of IEL (37%) are γ/δ T cells, whereas within LPL and PBL γ/δ T cells comprise a minor population (4.6% and 3.8% respectively). At these sites the number of γ/δ T cells labeled with anti‐CD8 mAb were 58.3% (IEL), 43.3% (LPL) and 24.4% (PBL). In situ staining of serial sections of large intestine confirmed these results. Hence, these data suggest a selective accumulation of CD8⁺ γ/δ T cells in the human epithelium of the large intestine. Furthermore, analysis of γ/δ TcR bearing IEL⁺ disclosed a marked preponderance of cells using the V_δ1 gene segment, whereas γ/δ TcR⁺ PBL preferentially express V_δ2. Strikingly, the majority of these V_δ1⁺ IEL bear the CDS molecule on their surface. These results are taken as evidence for a selective localization of V_δ1⁺ CD8⁺ γ/δ T cells in the epithelium of the large instestine.